title: Cytotoxic constituents from Celastrus paniculatus induce apoptosis and autophagy in breast cancer cells.
abstract: Celastrus paniculatus is a traditional medicinal plant with diverse pharmacological activities. To identify its bioactive constituents, three new β-dihydroagarofuranoid sesquiterpenes were isolated from the whole plant, of which the major constituent is (1α,2α,8β,9β)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-β-dihydroagarofuran. It was assessed for its antiproliferative activity, and it suppressed the viability of MCF-7 breast cancer cells with an IC50 of 17±1μM. This growth inhibition was, in part, attributable to apoptosis. Moreover, this drug treatment led to LC3B-II accumulation, indicative of autophagy. Western blot analysis established its ability to target a broad range of signaling effectors related to survival and cell cycle progression, including Akt, NF-κB, p53, and MAP kinases. In addition, flow cytometry analysis indicates increased reactive oxygen species production in response to this compound. Taken together, these findings suggest a pleiotropic mode of mechanism that underlies the antiproliferative activity of this compound in MCF-7 breast cancer cells.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan. columnster@gmail.com
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Weng
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Yen
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Lin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D031247:Celastrus / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C587585:(1alpha,2alpha,8beta,9beta)-1,8-bis(acetyloxy)-2,9-bis(benzoyloxy)-14-hydroxy-beta-dihydroagarofuran; D000972:Antineoplastic Agents, Phytogenic; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; C079978:dihydroagarofuran; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases
keywords: 4,6-diamidino-2-phenylindole; Apoptosis; Autophagy; CDK; Celastraceae; Celastrus paniculatus; DAPI; DMSO; ECL; ERK; FBS; LC3B; MAP kinases; PARP; PBS; SDS; Sesquiterpenes; cyclin-dependent kinase; dimethylsulfoxide; enhanced chemiluminescence; extracellular signal-regulated kinases; fetal bovine serum; microtubule-associated protein 1 light chain 3B; mitogen-activated protein kinases; phosphate buffered saline; poly ADP-ribose polymerase; sodium lauryl sulfate